A study of hospitalized COVID-19 patients with AKI in a setting of multiracial developing country.

BACKGROUND: The commonest indication for hospitalization in COVID-19 patients is hypoxemia or severe respiratory symptoms. However, COVID-19 disease may result in extrapulmonary complications including kidney-related pathology. The reported incidence of renal involvement related to COVID infection varies based on geographical location. OBJECTIVE: This study aimed to assess the incidence rate of AKI in hospitalized COVID-19 patients and identify risk factors and prognostic predictors. METHOD: In this retrospective study, we recruited hospitalized COVID-19 patients from January 2021 until June 2021 at the University Malaya Medical Center. The inclusion criteria were hospitalized for ≥ 48 h with confirmed COVID-19 infection and at least 18 years old. Patient demographic and clinical data were collected from electronic medical records. The staging of AKI was based on criteria as per KDIGO guidelines. RESULTS: One thousand five hundred twenty-nine COVID patients fulfilled the inclusion criteria with a male-to-female ratio of 759 (49.6%) to 770 (50.3%). The median age was 55 (IQR: 36-66). 500 patients (32.7%) had diabetes, 621 (40.6%) had hypertension, and 5.6% (n = 85) had pre-existing chronic kidney disease (CKD). The incidence rate of AKI was 21.1% (n = 323). The percentage of COVID patients in different AKI stages of 1,2 and 3 were 16.3%, 2.1%, and 2.7%, respectively. Fifteen hospitalized patients (0.98%) required renal replacement therapy. 58.8% (n = 190) of AKI group had complete recovery of kidney function. Demographic factors included age (p < 0.001), diabetes (p < 0.001), hypertension (p < 0.012), CKD (p < 0.001), and vaccination status (p = 0.042) were associated with an increased risk of developing AKI. We found that the AKI cohort had statistically significant lower platelet counts and higher ferritin levels than the non-AKI cohort. AKI is a risk predictor of prolonged hospitalization (p < 0.001) and higher mortality rates (P < 0.001). CONCLUSION: AKI is a common clinical complication among hospitalized COVID-19 patients. The etiology of AKI is multifactorial and may have an adverse impact on patient morbidity and mortality.

A longitudinal histologic evaluation of vitamin D receptor expression in the skeletal muscles of patients with a distal radius fracture.

We investigated the effect of vitamin D supplementation on the expression of muscle vitamin D receptor (VDR) and cross-sectional area (CSA) in patients with a distal radius fracture (DRF). Significant increases in VDR expression and CSA were observed, especially in vitamin D-deficient patients. PURPOSE: Vitamin D supplementation is known to enhance muscle mass and function, but whether the VDR is essential in this process remains unknown. We evaluated the change in VDR expression and CSA in the forearm muscles following vitamin D supplementation in patients with a DRF. METHODS: We prospectively recruited 18 women with a median age of 63.5 years who have a DRF. We obtained two biopsies of the forearm muscle, first at the time of fracture repair and then during hardware removal. We supplemented 1000 IU of vitamin D per day during a median interval of 8 months. We examined the changes in VDR expression and CSA by immunohistochemistry. RESULTS: The median serum 25-hydroxyvitamin D [25(OH)D] increased from 14.3 to 32.1 ng/mL (P = 0.001). The median VDR expression increased from 0.72 to 0.78 (P = 0.002), and the median CSA increased from 1290.0 to 1685.8 µm2 (P = 0.022). Significant increases in VDR expression and CSA were observed in vitamin D-deficient patients [25(OH)D] < 20 ng/mL, but not in vitamin D-non-deficient patients. The changes in VDR expression and CSA were in the same direction in 13 patients, but in the opposite direction in 5 patients. CONCLUSION: Vitamin D supplementation may increase muscle VDR expression and CSA in patients with a DRF, especially in vitamin D-deficient patients. The increase in CSA without an increase in VDR expression in some patients indicates that the effect of vitamin D supplementation on muscle mass could be mediated by indirect effect of serum vitamin D restoration and by VDR.

Using lactic acid bacteria and packaging with grapefruit seed extract for controlling Listeria monocytogenes growth in fresh soft cheese.

Various cheese products are involved in outbreaks of listeriosis worldwide due to high consumption and prolonged refrigerated storage. The objective of this study was to determine the efficacy of using lactic acid bacteria and packaging with grapefruit seed extract (GSE) for controlling Listeria monocytogenes growth in soft cheese. Leuconostoc mesenteroides and Lactobacillus curvatus isolated from kimchi were used as a starter culture to make a soft cheese, which was inoculated with a cocktail strain of L. monocytogenes. The soft cheese was packed with low-density polyethylene, biodegradable polybutylene adipate-co-terephthalate (PBAT), low-density polyethylene with GSE, or PBAT with GSE and stored at 10°C and 15°C. Leuconostoc mesenteroides (LcM) better inhibited the growth of L. monocytogenes than Lb. curvatus. The PBAT with GSE film showed the best control for the growth of L. monocytogenes. When both LcM and PBAT with GSE were applied to the soft cheese, the growth of L. monocytogenes was inhibited significantly more than the use of LcM or PBAT with GSE alone. In all test groups, water activity, pH, and moisture on a fat-free basis decreased, and titratable acidity increased compared with the control group. These results suggest that LcM isolated from kimchi and PBAT with GSE packaging film can be used as a hurdle technology to lower the risk of L. monocytogenes in soft cheese at the retail market.

Depth extraction with offset pixels.

Numerous depth extraction techniques have been proposed in the past. However, the utility of these techniques is limited as they typically require multiple imaging units, bulky platforms for computation, cannot achieve high speed and are computationally expensive. To counter the above challenges, a sensor with Offset Pixel Apertures (OPA) has been recently proposed. However, a working system for depth extraction with the OPA sensor has not been discussed. In this paper, we propose the first such system for depth extraction using the OPA sensor. We also propose a dedicated hardware implementation for the proposed system, named as the Depth Map Processor (DMP). The DMP can provide depth at 30 frames per second at 1920 × 1080 resolution with 31 disparity levels. Furthermore, the proposed DMP has low power consumption as for the aforementioned speed and resolution it only requires 290.76 mW. The proposed system makes it an ideal choice for depth extraction systems in constrained environments.

Screening Nuclear Field Fluctuations in Quantum Dots for Indistinguishable Photon Generation.

A semiconductor quantum dot can generate highly coherent and indistinguishable single photons. However, intrinsic semiconductor dephasing mechanisms can reduce the visibility of two-photon interference. For an electron in a quantum dot, a fundamental dephasing process is the hyperfine interaction with the nuclear spin bath. Here, we directly probe the consequence of the fluctuating nuclear spins on the elastic and inelastic scattered photon spectra from a resident electron in a single dot. We find the in-plane component of the nuclear Overhauser field leads to detuned Raman scattered photons, broadened over experimental time scales by field fluctuations, which are distinguishable from both the elastic and incoherent components of the resonance fluorescence. This significantly reduces two-photon interference visibility. However, we demonstrate successful screening of the nuclear spin noise, which enables the generation of coherent single photons that exhibit high visibility two-photon interference.

Kinetic studies of CO2 methanation over a Ni/γ-Al2O3 catalyst.

The production of methane by reacting CO2 with H2 (CO2 methanation) has the potential for producing synthetic natural gas, which could be exported using the existing infrastructure for the distribution of natural gas. The methanation of CO2 was investigated over a wide range of partial pressures of products and reactants using (i) a gradientless, spinning-basket reactor operated in batch mode and (ii) a laboratory-scale packed bed reactor operated continuously. The rate and selectivity of CO2 methanation, using a 12 wt% Ni/γ-Al2O3 catalyst, were explored at temperatures 445-497 K and pressures up to 20 bar. Research with the batch reactor showed that the rate increased with increasing partial pressures of H2 and CO2 when the partial pressures of these reactants were low; however, the rate of reaction was found to be insensitive to changes in the partial pressures of H2 and CO2 when their partial pressures were high. A convenient method of determining the effect of H2O on the rate of reaction was also developed using the batch reactor and the inhibitory effect of H2O on CO2 methanation was quantified. The kinetic measurements were compared with a mathematical model of the reactor, in which different kinetic expressions were explored. The kinetics of the reaction were found to be consistent with a mechanism in which adsorbed CO2 dissociated to adsorbed CO and O on the surface of the catalyst with the rate-limiting step being the subsequent dissociation of adsorbed CO. The ability of the kinetic expressions to predict the results from the continuous, packed-bed reactor was explored, with some discrepancies discussed.

The prognostic significance of pretreatment [18F]FDG-PET/CT imaging in patients with uterine cervical cancer: preliminary results.

PURPOSE OF INVESTIGATION: To evaluate the prognostic significance of positron emission tomography/computed tomography (PET/CT) in patients diagnosed with cervical cancer. MATERIALS AND METHODS: Patients with cervical cancer in FIGO Stages IB1 to IVB were imaged with PET/CT prior to treatment during one of the staging work-ups. The patients were observed for a median of 31.4 months (range, six to 89 months) after the initial treatment. The standardized uptake value (SUV) max of the primary cervical tumor mass was compared with the prognostic factors. RESULTs: A total of 81 patients who were primarily treated with radical hysterectomy (RH, n = 45) or concurrent chemoradiation (CCRT, n = 36) were analyzed. Multivariate analysis indicated that larger tumor size (> 4 cm, OR 8.694, 95% CI, 1.638-46.146), deep stromal invasion (≥ 1 cm, OR 7.249, 95% CI, 1.141-46.039) by the primary tumor, and pathologically confirmed pelvic lymph node involvement (positive, OR 14.586, 95% CI, 2.072-102.674) were significantly associated with recurrence after treatment. However, pretreatment SUVmax was not a significant independent predictor of disease recurrence (OR 1.058, 95% CI, 0.255-4.398). CONCLUSION: [18F]Fluorodeoxyglucose (FDG) uptake by the primary tumor showed a significant association with several risk factors that have been identified as treatment predictors. However, a high pretreatment SUVmax was not predictive of recurrence in uter- ine cervical cancer patients.

Fabrication of GaAs/Al0.3Ga0.7As multiple quantum well nanostructures on (100) si substrate using a 1-nm InAs relief layer.

Nanometer scale thin InAs layer has been incorporated between Si (100) substrate and GaAs/Al0.3Ga0.7As multiple quantum well (MQW) nanostructure in order to reduce the defects generation during the growth of GaAs buffer layer on Si substrate. Observations based on atomic force microscopy (AFM) and transmission electron microscopy (TEM) suggest that initiation and propagation of defect at the Si/GaAs interface could be suppressed by incorporating thin (1 nm in thickness) InAs layer. Consequently, the microstructure and resulting optical properties improved as compared to the MQW structure formed directly on Si substrate without the InAs layer. It was also observed that there exists some limit to the desirable thickness of the InAs layer since the MQW structure having thicker InAs layer (4 nm-thick) showed deteriorated properties.

Multifocal microinvasive squamous cell carcinoma with extensive spread of squamous cell carcinoma in situ (CIS) into the uterine corpus, vagina, and left salpinx diagnosed five years after conization of cervical CIS.

BACKGROUND: Multifocal microinvasive squamous cell carcinoma (SCC) with extensive spread of squamous cell carcinoma in situ (CIS) into the uterine corpus, salpinx, and vagina is extremely unusual. CASE: The authors present a case of 69-year-old woman with hydrometra who was found to have multifocal microinvasive SCC in the endometrium. The CIS had spread superficially throughout the entire endometrium up to the fundus, completely replacing the epithelium. The uterine cervix, vaginal surface and left salpingeal mucosa were involved. She had previously undergone conization due to cervical CIS five years prior. The pathologic reports showed clear resection margins at that time. CONCLUSION: The present case suggests that CIS in the endometrium spread back to the cervix and vagina, although the definite origin of the first CIS was not determined.

Enhanced oxidative damage to DNA, lipids, and proteins and levels of some antioxidant enzymes, cytokines, and heat shock proteins in patients infected with influenza H1N1 virus.

Overweight and obesity is becoming widespread enough to generate an acceptable and misleading social status. By 2030, in the USA up to 86 % of adults will be overweight or obese. Some selected statistical data based on the body mass index (BMI) indicated that overweight was not associated with increased mortality, this provoked a conceivable interest. Added to this is the observation that while the prevalence of obesity is dramatically increasing, the cardiovascular mortality and life expectancy in the European Union and USA has improved. When more sensitive indicators of body adiposity and its distribution than the BMI, like the waist-thigh ratio in both sexes and the waist-hip ratio in women are projected on mortality, it becomes obvious that even overweight is associated with an increased health risk. Gaining excessive body fat is a continuous, frequently progressive process. Present obesity epidemic in childhood will manifest with deleterious consequences only in future years when adolescents reach adulthood. Prevention is thus essential even before the overweight sets in. Improved life expectancy observed in large populations despite obesity epidemic, is a favourable medical success in the management of hypertension, of serum lipid disorders and diabetes. While encouraging, when it is observed in large population, it does not take away the potential health risk of a metabolic disorder in an individual who is overweight (Fig. 7, Ref. 25).

Thoracic vessel injury.

Thoracic trauma occurs in an estimated 25% of all trauma victims, with approximately 50% of trauma mortalities attributable to these injuries. Only 4% of thoracic traumas involve injuries to thoracic vessels, including the aorta, innominate veins and artery, left carotid artery, internal mammaries, and pulmonary hilar vessels. These vascular injuries can range from minor to major with advances in prehospital management increasing the number of patients surviving in the field and presenting to the hospital with life-threatening vascular injuries. Rapid assessment during the initial survey and interventions to maintain airway, breathing, and circulation of the patient can be life-saving. The patient's hemodynamic status will often dictate the extent of the initial workup or whether the patient requires emergent operation. Stable patients can undergo further assessment and detailed imaging, such as computed tomography and/or angiography. Treatment of thoracic vessel injuries may include advanced endovascular techniques, traditional open surgery, or non-operative management with observation. The following review systematically details the initial workup, evaluation and management techniques of thoracic vessel injuries.

Killed but metabolically active microbes: a new vaccine paradigm for eliciting effector T-cell responses and protective immunity.

We developed a new class of vaccines, based on killed but metabolically active (KBMA) bacteria, that simultaneously takes advantage of the potency of live vaccines and the safety of killed vaccines. We removed genes required for nucleotide excision repair (uvrAB), rendering microbial-based vaccines exquisitely sensitive to photochemical inactivation with psoralen and long-wavelength ultraviolet light. Colony formation of the nucleotide excision repair mutants was blocked by infrequent, randomly distributed psoralen crosslinks, but the bacterial population was able to express its genes, synthesize and secrete proteins. Using the intracellular pathogen Listeria monocytogenes as a model platform, recombinant psoralen-inactivated Lm DeltauvrAB vaccines induced potent CD4(+) and CD8(+) T-cell responses and protected mice against virus challenge in an infectious disease model and provided therapeutic benefit in a mouse cancer model. Microbial KBMA vaccines used either as a recombinant vaccine platform or as a modified form of the pathogen itself may have broad use for the treatment of infectious disease and cancer.

A study protocol for a double-blind randomised placebo-controlled trial evaluating the efficacy of carrageenan nasal and throat spray for COVID-19 prophylaxis-ICE-COVID.

INTRODUCTION: At present, vaccines form the only mode of prophylaxis against COVID-19. The time needed to achieve mass global vaccination and the emergence of new variants warrants continued research into other COVID-19 prevention strategies. The severity of COVID-19 infection is thought to be associated with the initial viral load, and for infection to occur, viruses including SARS-CoV-2 must first penetrate the respiratory mucus and attach to the host cell surface receptors. Carrageenan, a sulphated polysaccharide extracted from red edible seaweed, has shown efficacy against a wide range of viruses in clinical trials through the prevention of viral entry into respiratory host cells. Carrageenan has also demonstrated in vitro activity against SARS-CoV-2. METHODS AND ANALYSIS: A single-centre, randomised, double-blinded, placebo-controlled phase III trial was designed. Participants randomised in a 1:1 allocation to either the treatment arm, verum Coldamaris plus (1.2 mg iota-carrageenan (Carragelose®), 0.4 mg kappa-carrageenan, 0.5% sodium chloride and purified water), or placebo arm, Coldamaris sine (0.5% sodium chloride) spray applied daily to their nose and throat for 8 weeks, while completing a daily symptom tracker questionnaire for a total of 10 weeks. PRIMARY OUTCOME: Acquisition of COVID-19 infection as confirmed by a positive PCR swab taken at symptom onset or seroconversion during the study. Secondary outcomes include symptom type, severity and duration, subsequent familial/household COVID-19 infection and infection with non-COVID-19 upper respiratory tract infections. A within-trial economic evaluation will be undertaken, with effects expressed as quality-adjusted life years. DISCUSSION: This is a single-centre, phase III, double-blind, randomised placebo-controlled clinical trial to assess whether carrageenan nasal and throat spray reduces the risk of development and severity of COVID-19. If proven effective, the self-administered prophylactic spray would have wider utility for key workers and the general population. TRIAL REGISTRATION: NCT04590365; ClinicalTrials.gov NCT04590365. Registered on 19 October 2020.

Elastic properties of polycaprolactone at small strains are significantly affected by strain rate and temperature.

Tensile tests were conducted on polycaprolactone at various strain rates and temperatures. Focusing on the mechanical properties within only the small-strain elastic region, i.e. up to the inflection point in the stress-strain diagram, it was found that strain rate and temperature had significant effects on the polymer. This finding implies that the effects of strain rate and temperature on the elastic properties of polycaprolactone should be considered in the design and manufacture of rigidity-sensitive, load-bearing applications, including use as biomaterial for scaffolds in tissue engineering applications.

Slow Gait, Subjective Cognitive Decline and Motoric Cognitive RISK Syndrome: Prevalence and Associated Factors in Community Dwelling Older Adults.

BACKGROUND: Motoric Cognitive Risk Syndrome (MCR), slow gait speed (SG) and subjective cognitive decline (SCD) are known to be harbingers of dementia. MCR is known to be associated with a 3-fold increased risk of future dementia, while SG can precede cognitive impairment. OBJECTIVE: We aim to determine the prevalence and demographics of MCR, slow gait alone (SG-A) and subjective cognitive decline alone (SCD-A) in community-dwelling older adults and association with physical, functional, cognition and psychosocial factors. METHODS: A total of 509 participants were classified into four groups according to presence of SG and/or SCD. Multinomial logistic regression was used to identify the factors associated with SG-A, SCD-A and MCR. RESULTS: The prevalence of MCR was 13.6%, SG-A 13.0% and SCD-A 35.0%. Prevalence of MCR doubled every decade in females with 27.7% of female ≥ 80 years old had MCR. Almost 4 in 10 had no SG or SCD (SG+SCD negative). MCR and SG-A groups were significantly older, had higher body mass index (BMI), lower education, lower global cognition scores especially in non-memory domains, higher prevalence of low grip strength and lower short physical performance battery scores than those with SCD-A and SG+SCD negative. In addition, the SG-A group had significantly higher prevalence of multi-morbidity and diabetes. The prevalence of pain, depression, frailty, social isolation and activity of daily living impairment were significantly higher in MCR. The global cognitive and functional scores for those with SCD-A were comparable to the SG+SCD negative group. The Malay ethnic group had the lowest prevalence of SCD but highest prevalence of SG. After adjusting for confounding factors, age, BMI, frailty status, instrumental activity of daily living, depression and pain remained significantly associated with MCR. For SG-A, age, BMI, education and number of chronic diseases remained significant. CONCLUSION: Both MCR and SG-A are associated with global cognitive decline especially in the non-memory domains and lower functional scores. Gait speed is a good predictor of negative outcomes and should be considered as the 'sixth' vital sign. Long term prospective studies are needed to evaluate: i) the conversion to dementia in different ethnic groups and ii) effect of targeted physical and / or dual task exercise on delaying the conversion to dementia and / or improvement in physical measures and reduction of disability.

Frailty and Quality of Life in Older Adults with Metabolic Syndrome - Findings from the Healthy Older People Everyday (HOPE) Study.

OBJECTIVES: Metabolic syndrome (MetS) and frailty are both associated with increased morbidity and mortality. Frailty is associated with reduced quality of life (QoL) but association of QoL with MetS have produced mixed results suggesting that other factors such as disease burden, obesity and depression may have a more significant influence. We aim to investigate the demographics of frail participants with MetS, and relationship between frailty and QoL in MetS. METHODS: Cross-sectional population study involving 292 older adults ≥ 65 years with MetS. MetS was defined using the Modified ATP III for Asians which requires the presence of 3 or more of the following 5 components 1) waist circumference ≥ 90cm for males or ≥ 80cm for females, 2) TG ≥ 150mg/dL, 3) HDLc < 40mg/dL in males or < 50mg/dL in females, 4) blood pressure ≥ 130/85mmHg or use of anti-hypertensive medication, and 5) fasting plasma glucose ≥ 100mg/dL or use of pharmacological treatment for diabetes mellitus. Data were collected on demographics, frailty (FRAIL), QoL (Euroqol-5D), perceived health, functional status, cognition, Timed-Up-and-Go (TUG), and hand-grip strength (HGS). RESULTS: 40.4% of the participants were pre-frail (MetSprefrail) and 7.2% were frail (MetSfrail). MetSfrail were significantly older, had lower education level, higher polypharmacy burden and higher prevalence of diabetes. The prevalence of at least 1 activity of daily living impairment was 4 times higher, and depression 9 times higher than their robust counterparts. MetSfrail also had longer TUG, higher prevalence of poor grip strength and poor perceived health. After adjusting for age, gender and education, MetSfrail was significantly associated with much higher odds of EQ-5D moderate to extreme problems with mobility (Odds Ratio (OR) =10.99, CI 2.62-46.14), usual activities (OR=37.82, CI 3.77-379.04) and pain (OR=10.79, CI 3.18-36.62). EQ-5D Index Value and Perceived Health improved by 0.1 (Mean Difference (MD) =0.07, CI 0.04-0.10) and 6.0 (MD=6.01, CI 3.29-8.73) respectively as frailty status improved. CONCLUSION: Frailty in MetS is associated with depression, polypharmacy, greater functional impairment, poorer QoL and perceived health. Frailty screening and personalized management is crucial in MetS as frailty may be a mediator for negative outcomes in MetS, and frailty may be reversible.

Association of Pain and Impact of Dual-Task Exercise on Function, Cognition and Quality of Life.

PURPOSE: This study aimed to assess the factors associated with pain and evaluate the impact of dual-task exercise on pain improvement, quality of life (QOL), cognition and function in older adults. PATIENTS AND METHODS: This study is a secondary data analysis of the HAPPY (Healthy Ageing Promotion Program for You) study. At risk older adults ≥ 60 years old were enrolled in a community dual-task exercise program. Assessments for frailty, sarcopenia, falls, quality of life (QOL) and perceived health, depression, cognition and physical function were performed at baseline and 3 months. Pain intensity was derived from EQ-5D and stratified into no pain, slight pain and moderate to extreme pain. RESULTS: Out of 296 participants, 37.2% had slight pain and 11.1% had moderate to severe pain. Both slight and moderate to extreme pain compared with no pain group were significantly associated with lower perceived health (68.2,63.6 vs 76.0) and QOL index (0.70,0.59 vs 0.93); moderate to extreme pain was also significantly associated with depression, low mental vitality, frailty, sarcopenia and poorer physical performance. After 3 months of dual-task exercise, pain improved in 70.8% of the moderate to extreme pain group and 50.8% of slight pain group. Significant improvement in perceived health, QOL, physical function and cognition were also observed. CONCLUSION: Proactive efforts are required to screen for pain and manage frailty, sarcopenia and depression. Dual-task exercise proved safe and possibly effective in reducing pain and improving QOL, physical and cognitive function in older adults. Prospective randomized studies are needed to validate the effectiveness of dual-task vs single-task exercise, including impact of reversal of frailty and sarcopenia in pain management.

Retroductal Delivery of Epidermal Growth Factor Protects Salivary Progenitors after Irradiation.

Salivary gland hypofunction after irradiation is associated with a deficit of epithelial stem/progenitors in salivary glands. Although epidermal growth factor (EGF) is known to stimulate the proliferation of epithelial cells, the therapeutic effect of EGF on salivary epithelial stem/progenitors remains undetermined. In this study, we administered EGF to submandibular glands (SMGs) via a retrograde route through the SMG excretory duct before fractionated irradiation and examined whether EGF could protect salivary epithelial progenitor cells from radiation and alleviate radiation-induced salivary hypofunction. EGF-treated mice exhibited greater body and gland weights at 12 wk after irradiation than untreated mice. The retroductal delivery of EGF improved salivary secretory function and increased salivary amylase activity in a dose-dependent manner. Histological examinations highlighted the amelioration of the loss of keratine-14+ (KRT14+) basal ductal and/or MIST1+ acinar cells, as well as induction of fibrosis, following irradiation in EGF-treated mice. An additional in vitro experiment using a salivary gland organoid irradiation model indicated that the radioprotective effects of EGF promoted the growth and inhibited the apoptotic cell death of salivary epithelial cells. Our results suggest that retroductal delivery of EGF may be a promising therapeutic option for preventing radiation-induced salivary gland hypofunction.

Branched oligomerization of cell-permeable peptides markedly enhances the transduction efficiency of adenovirus into mesenchymal stem cells.

Cell-permeable peptides (CPPs) promote the transduction of nonpermissive cells by recombinant adenovirus (rAd) to improve the therapeutic efficacy of rAd. In this study, branched oligomerization of CPPs significantly enhanced the transduction of human mesenchymal stem cells (MSCs) by rAd in a CPP type-independent manner. In particular, tetrameric CPPs increased transduction efficiency at 3000-5000-fold lower concentrations than did monomeric CPPs. Although branched oligomerization of CPPs also increases cytotoxicity, optimal concentrations of tetrameric CPPs required for maximum transduction are at least 300-1000-fold lower than those causing 50% cytotoxicity. Furthermore, although only approximately 60% of MSCs were maximally transduced at 500 muM of monomeric CPPs, >95% of MSCs were transduced with 0.1 muM of tetrameric CPPs. Tetrameric CPPs also significantly increased the formation and net surface charge of CPP/rAd complexes, as well as the binding of rAd to cell membranes at a greater degree than did monomeric CPPs, followed by rapid internalization into MSCs. In a critical-size calvarial defect model, the inclusion of tetrameric CPPs in ex vivo transduction of rAd expressing bone morphogenetic protein 2 into MSCs promoted highly mineralized bone formation. In addition, MSCs that were transduced with rAd expressing brain-derived neurotrophic factor in the presence of tetrameric CPPs improved functional recovery in a spinal cord injury model. These results demonstrated the potential for tetrameric CPPs to provide an innovative tool for MSC-based gene therapy and for in vitro gene delivery to MSCs.

Assessment of post-stroke extrapersonal neglect using a three-dimensional immersive virtual street crossing program.

OBJECTIVE: To investigate the potential of our newly developed three-dimensional immersive virtual reality (VR) program modeled on a real street crossing as an assessment tool for extrapersonal neglect in stroke patients. METHODS: Thirty-two patients with right-hemispheric stroke (neglect group, 16; non-neglect group, 16) were enrolled. The deviation angle, reaction time, left-to-right reaction time ratio, visual and auditory cue rates, and failure rate were evaluated during missions to keep a virtual avatar safe from a traffic accident in the VR program. The line bisection test and letter cancellation test were also evaluated. RESULTS: The deviation angle, left-to-right reaction time ratio, left visual and auditory cue rates and left failure rate in the VR program showed significant differences between the two groups (P < 0.05). Depending on the direction of approach of the virtual car, the left parameters were significantly higher than the right parameters in the neglect group (P < 0.05). In the neglect group, the line bisection test correlated significantly with the deviation angle (P < 0.05). None of the other virtual reality parameters significantly correlated with the paper and pencil tests. CONCLUSION: Post-stroke neglect in the extrapersonal space can be easily and safely detected and measured using our three-dimensional immersive virtual street crossing program.